Formation of free radicals of oxygen may explain many of the deleterious effects of exposure to high concentrations of this gas. The extreme reactivity of these radicalized molecules could lead to molecular damage characteristic of oxygen poisoning. A number of studies have shown that the superoxide dismutases may protect against oxygen toxicity by dismuting the superoxide free radical. Our laboratory has concentrated on determining the role of the superoxide dismutases in the development of oxygen adaptation in the adult rat. Biochemical studies have shown that both the Copper-zinc and Manganese containing superoxide dismutases are increased in the lungs of oxygen adapted rats. Qualitative and quantitative pathological studies have precisely defined the changes in cell number and cell mass occurring in the lungs of these animals, and we have found evidence suggesting that hypertrophy of endothelial cells is an essential part of the process of adaptation. This proposal is for funds to develop immunocytochemical techniques to localize the superoxide dismutases in intact lung tissue. These techniques will be used to define which cells are rich in each of these enzymes and to define the subcellular localization of the superoxide dismutases. The changes which occur in the cellular and subcellular distribution of these enzymes after exposure to hyperoxia will be evaluated and correlated with our previous biochemical and morphometric studies.